Malaria and HIV are two of the most important Infectious diseases worldwide that are overlapping and synergistic in sub-Saharan Africa. Despite the scale up of front line prevention efforts, the burden of malaria remains staggering among pregnant women and children; and malnutrition and growth retardation are major threats to child health. The purpose of the Prevention of Malaria and HIV Disease in Tororo (PROMOTE) program project (POI) is to evaluate promising interventions to reduce the burden of malaria and HIV and Improve maternal-child health through hypothesis based intervention studies. PROMOTE II will test the hypotheses that a) enhanced malaria chemoprevention in HIV infected and uninfected pregnant women will reduce placenta malaria; b) enhanced chemoprevention provided during both pregnancy and childhood will reduce malaria in children in the first 2 years of life and c) limiting in utero exposure to malaria antigens with enhanced malaria chemoprevention during pregnancy will reduce development of fetal immune tolerance to malaria antigens. The proposed clinical studies will evaluate chemoprevention with dihydroartemisinin-piperaquine (DP), a new artemisinin combination therapy (ACT), established as highly safe and effective for malaria treatment in pregnant women and children. PROMOTE II consists of 3 projects and 3 cores. There are 2 interlinked double blinded, randomized controlled trials in HIV-uninfected pregnant women (Project 1), and HIV-infected pregnant women (Project 2) and the children born to them with parallel structure that permits comparisons in malaria, immune responses and pharmacokinetics of DP between populations with differing HIV status and exposure. Project 3 is laboratory based, and is focused on testing central hypothesis of malaria immunity using well characterized specimens from the 2 clinical trials. Administrative, laboratory, and data cores provide infrastructure support to the projects, including the capacity to process and evaluate placental malaria using histopathology.